Improvements in Cardiac Spect/CT for the Purpose of Tracking Transplanted Cells

Regenerative therapy via stem cell transplantation has received increased attention to help treat the myocardial injury associated with heart disease. Currently, the hybridisation of SPECT with X-ray CT is expanding the utility of SPECT. This thesis compared two SPECT/CT systems for attenuation correction using slow or fast-CT attenuation maps (mu-maps). We then developed a method to localize transplanted cells in relation to compromised blood flow in the myocardium following a myocardial infarction using SPECT/CT. Finally, a method to correct for image truncation was studied for a new SPECT/CT design that incorporated small field-of-view (FOV) detectors. Computer simulations compared gated-SPECT reconstructions using slow-CT and fast-CT mu-maps with gated-CT mu-maps. Using fast-CT mu-maps improved the Root Mean Squared (RMS) error from 4.2% to 4.0%. Three canine experiments were performed comparing SPECT/CT reconstruction using the Infinia/Hawkeye-4 (slow-CT) and Symbia T6 (fast-CT). Canines were euthanized prior to imaging, and then ventilated. The results showed improvements in both RMS errors and correlation coefficients for all canines. A first-pass contrast CT imaging technique can identify regions of myocardial infarction and can be fused with SPECT. Ten canines underwent surgical ligation of the left-anterior-descending artery. Cells were labeled with 111In-tropolone and transplanted into the myocardium. SPECT/CT was performed on day of transplantation, 4, and 10 days post-transplantation. For each imaging session first-pass perfusion CT was performed and successfully delineated the infarct zone. Delayed-enhanced MRI was performed and correlated well with first-pass CT. Contrast-to-noise ratios were calculated for 111In-SPECT and suggested that cells can be followed for 11 effective half-lives. We evaluated a modified SPECT/CT acquisition and reconstruction method for truncated SPECT. Cardiac SPECT/CT scans were acquired in 14 patients. The original projections were truncated to simulate a small FOV acquisition. Data was reconstructed in three ways: non-truncated and standard reconstruction (NTOSEM), which was our gold-standard; truncated and standard reconstruction (TOSEM); and truncated and a modified reconstruction (TMOSEM). Compared with NTOSEM, small FOV imaging incurred an average cardiac count ratio error greater than 100% using TOSEM and 8.9% using TMOSEM. When we plotted NTOSEM against TOSEM and TMOSEM the correlation coefficient was 0.734 and 0.996 respectively

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

nuclear medicine; diagnostic radiolog

Theoretical and numerical study of MLEM and OSEM reconstruction algorithms for motion correction in emission tomography

Patient body-motion and respiratory-motion impacts the image quality of cardiac SPECT and PET perfusion images. Several algorithms exist in the literature to correct for motion within the iterative maximum-likelihood reconstruction framework. In this work, three algorithms are derived starting with Poisson statistics to correct for patient motion. The first one is a motion compensated MLEM algorithm (MC-MLEM). The next two algorithms called MGEM-1 and MGEM-2 (short for Motion Gated OSEM, 1 and 2) use the motion states as subsets, in two different ways. Experiments were performed with NCAT phantoms (with exactly known motion) as the source and attenuation distributions. Experiments were also performed on an anthropomorphic phantom and a patient study. The SIMIND Monte Carlo simulation software was used to create SPECT projection images of the NCAT phantoms. The projection images were then modified to have Poisson noise levels equivalent to that of clinical acquisition. We investigated application of these algorithms to correction of (1) a large body-motion of 2 cm in Superior-Inferior (SI) and Anterior-Posterior (AP) directions each and (2) respiratory motion of 2 cm in SI and 0.6 cm in AP. We determined the bias with respect to the NCAT phantom activity for noiseless reconstructions as well as the bias-variance for noisy reconstructions. The MGEM-1 advanced along the bias-variance curve faster than the MC-MLEM with iterations. The MGEM-1 also lowered the noiseless bias (with respect to NCAT truth) faster with iterations, compared to the MC-MLEM algorithms, as expected with subset algorithms. For the body motion correction with two motion states, after the 9th iteration the bias was close to that of MC-MLEM at iteration 17, reducing the number of iterations by a factor of 1.89. For the respiratory motion correction with 9 motion states, based on the noiseless bias, the iteration reduction factor was approximately 7. For the MGEM-2, however, bias-plot or the bias-variance-plot saturated with iteration because of successive interpolation error. SPECT data was acquired simulating respiratory motion of 2 cm amplitude with an anthropomorphic phantom. A patient study acquired with body motion in a second rest was also acquired. The motion correction was applied to these acquisitions with the anthropomorphic phantom and the patient study, showing marked improvements of image quality with the estimated motion correction. © 2009 IEEE

Implementation of GPU accelerated SPECT reconstruction with Monte Carlo-based scatter correction

Statistical SPECT reconstruction can be very time-consuming especially when compensations for collimator and detector response, attenuation, and scatter are included in the reconstruction. This work proposes an accelerated SPECT reconstruction algorithm based on graphics processing unit (GPU) processing. Ordered subset expectation maximization (OSEM) algorithm with CT-based attenuation modelling, depth-dependent Gaussian convolution-based collimator-detector response modelling, and Monte Carlo-based scatter compensation was implemented using OpenCL. The OpenCL implementation was compared against the existing multi-threaded OSEM implementation running on a central processing unit (CPU) in terms of scatter-to-primary ratios, standardized uptake values (SUVs), and processing speed using mathematical phantoms and clinical multi-bed bone SPECT/CT studies. The difference in scatter-to-primary ratios, visual appearance, and SUVs between GPU and CPU implementations was minor. On the other hand, at its best, the GPU implementation was noticed to be 24 times faster than the multi-threaded CPU version on a normal 128 x 128 matrix size 3 bed bone SPECT/CT data set when compensations for collimator and detector response, attenuation, and scatter were included. GPU SPECT reconstructions show great promise as an every day clinical reconstruction tool.Peer reviewe

An investigation into the limitations of myocardial perfusion imaging

Myocardial Perfusion Imaging (MPI) plays a very important role in the management of patients with suspected Coronary Artery Disease and its use has grown despite the shortcomings of the technique. Significant progress has been made in identifying the causes of these shortcomings and many solutions been suggested in the literature but the clinical sensitivity and specificity of the technique is still well below optimum. Monte Carlo Simulation is a very useful tool in identifying and guiding the understanding of the existing problems in MPI and this present study utilised this method to establish the basis of the simulations to be used and the way to analyse the results so that many of the causes of the attenuation defects, when using MPI, could be identified. This was achieved by investigating the effect that the different anatomical parts of the thorax have on the attenuation defects caused. A further aspect investigated was the impact that self-absorption in the heart has on these defects. The variability of these defects were further investigated by altering the position and orientation of the heart itself within the thorax and determining the effect it has on the attenuation defects caused. Results indicate that the attenuation caused is a very complicated process, that the self-absorption of the heart plays an extremely important role and the impact of the different positions and orientation of the heart inside the thorax are also significant. The distortion caused on the images by these factors was demonstrated by the intensity losses in the basal part and an over-estimation in the apical parts, which were clearly observable on the final clinical images, with the potential to affect clinical interpretation. Attenuation correction procedures using transmission sources, have been available for some time, but have not been adopted widely, amidst concern that they introduce additional artefacts. This study determined the effectiveness of these methods by establishing the level of correction obtained and whether additional artefacts were introduced. This included the effectiveness of the compensation achieved with the use of the latest commercially available comprehensive correction techniques. The technique investigated was “Flash3D" from Siemens providing transmission based attenuation correction, depth-dependent resolution recovery and scatter correction. The comparison between the defects and intensity losses predicted by the Monte Carlo Simulations and the corrections provided by this commercial correction technique revealed that solution is compensating almost entirely for these problems and therefore do provide substantial progress in overcoming the limitations of MPI. As a result of the improvements gained from applying these commercially available techniques and the accuracy established in this study for the mentioned technique it is strongly recommended that these new techniques be embraced by the wider Nuclear Medicine community so that the limitations in MPI can be reduced in clinical environment. Non-withstanding the above gains made there remains room for improvement by overcoming the of use transmission attenuation correction techniques by replacing them with emission based techniques. In this study two new related emission based attenuation correction techniques have been suggested and investigated and provide a promising prospect of overcoming these limitations

Estimation of the rigid-body motion from three-dimensional images using a generalized center-of-mass points approach

We present an analytical method for the estimation of rigid-body motion in sets of three-dimensional (3-D) SPECT and PET slices. This method utilizes mathematically defined generalized center-of-mass points in images, requiring no segmentation. It can be applied to compensation of the rigid-body motion in both SPECT and PET, once a series of 3-D tomographic images are available. We generalized the formula for the center-of-mass to obtain a family of points comoving with the object\u27s rigid-body motion. From the family of possible points we chose the best three points which resulted in the minimum root-mean-square difference between images as the generalized center-of-mass points for use in estimating motion. The estimated motion was used to sum the sets of tomographic images, or incorporated in the iterative reconstruction to correct for motion during reconstruction of the combined projection data. For comparison, the principle-axes method was also applied to estimate the rigid-body motion from the same tomographic images. To evaluate our method for different noise levels, we performed simulations with the MCAT phantom. We observed that though noise degraded the motion-detection accuracy, our method helped in reducing the motion artifact both visually and quantitatively. We also acquired four sets of the emission and transmission data of the Data Spectrum Anthropomorphic Phantom positioned at four different locations and/or orientations. From these we generated a composite acquisition simulating periodic phantom movements during acquisition. The simulated motion was calculated from the generalized center-of-mass points calculated from the tomographic images reconstructed from individual acquisitions. We determined that motion-compensation greatly reduced the motion artifact. Finally, in a simulation with the gated MCAT phantom, an exaggerated rigid-body motion was applied to the end-systolic frame. The motion was estimated from the end-diastolic and end-systolic images, and used to sum them into a summed image without obvious artifact. Compared to the principle-axes method, in two of the three comparisons with anthropomorphic phantom data our method estimated the motion in closer agreement to the Polaris system than the principal-axes method, while the principle-axes method gave a more accurate estimation of motion in most cases for the MCAT simulations. As an image-driven approach, our method assumes angularly com plete data sets for each state of motion. We expert this method to be applied in correction of respiratory motion in respiratory gated SPECT, and respiratory or other rigid-body motion in PET. © 2006 IEEE

Optimization of activity level in rCBF SPECT using the observer study Visual Grading Regression

The purpose of this work is to assess the activity level needed to achieve satisfactory diagnostic information in regional cerebral blood flow single photon emission computed tomography (rCBF SPECT) by introducing a new evaluation method to be used for and hopefully facilitate optimization studies in nuclear medicine in the future. The purpose is further to perform a visual grading study and investigate the use of this new evaluation method, Visual Grading Regression (VGR). Image quality criteria applicable to rCBF SPECT images will be defined in this work and their relevance for evaluating rCBF SPECT image quality is investigated. The study comprises a material of 21 consecutive patients with dementia issue that have undergone an rCBF SPECT examination. An administered activity of 1000 MBq 99mTc labelled HMPAO was injected to all patients in the study. From one single examination, five studies corresponding to different activity levels (500, 625, 750, 875 and 1000 MBq) were generated by using a gated acquisition. Iterative image reconstruction, OS-EM, including corrections for attenuation, scatter and distance dependent resolution was used. Three experienced observers, i.e. specialists in nuclear medicine, evaluated the images by rating their confidence about the fulfilment of specific image quality criteria. Seven criteria were defined in this study, developed in collaboration with experienced specialists in nuclear medicine with comprehensive knowledge on how to evaluate rCBF SPECT images. The result of the observers assessment were analysed using Visual Grading Regression, a method based on ordinal logistic regression with the aim to analyse data from visual grading experiments. The result shows that there is a significant difference in perceived image quality between 500 MBq and the reference activity, 1000 MBq, in five of the seven image quality criteria. No statistical significant degradation was found between any other activity level than 500 MBq and the reference activity (1000 MBq). This study doesn’t prove that any other activity level provides the same image quality as 1000 MBq, only because no difference was seen, but it gives an indication that the activity level could be reduced without losing too much diagnostic information. The analysis method used, Visual Grading Regression, has proven to be convenient and easy to use for this kind of optimisation studies in nuclear medicine. The defined criteria cover the areas of the brain that are of interest in blood flow examinations and the results of this study showed that the observers used the whole confidence rating scale for each criterion, which is desirable. Some of the criteria had a very low proportion of rating scores corresponding to a fulfilment of the criterion, meaning that the satisfaction of the observers is low. A reversion or adjustment of these criteria might be needed to investigate whether the low satisfaction level is due to the formulation of the criteria or if only so the particular area is difficult to assess.Möjligheten att visualisera olika sjukdomstillstånd med hjälp av bilder har inom sjukvården blivit mer och mer populärt. Nuklearmedicinska bilder framställs genom att en liten mängd av ett radioaktivt ämne injiceras i patienten och sedan detekteras med hjälp av en gammakamera. Genom att utnyttja olika upptagsmekanismer kan funktionen av ett område eller ett specifikt organ i kroppen undersökas. Blodflödet i hjärnan kan studeras genom att injicera ett radioaktivt ämne som är kopplat till en fettmolekyl, vilken passerar blod-hjärnbarriären och ackumuleras i hjärnan. Upptaget av det radioaktiva ämnet avspeglar det regionala blodflödet i hjärnan vid tidpunkten för injektionen eller strax därefter. Regionala blodflödesstudier i hjärnan utförs på patienter som stöd vid diagnostisering av demenssjukdomar då flertalet av dessa leder till en minskning av det regionala blodflödet i hjärnan. Aktivitetsmängden som injiceras påverkar både bildkvaliteten och stråldosen till patienten. För att säkerställa den aktivitet som krävs för att ge tillräckligt god bildkvalitet till lägsta möjliga stråldos krävs ett optimeringsarbete. Detta görs vanligtvis med hjälp av fysikaliska parametrar såsom brus, upplösning och kontrast. Ett annat sätt att bedöma bildkvalitet är med hjälp av erfarna observatörer som gör en visuell bedömning utifrån kliniskt relevanta bildkriterier. I arbetet introduceras en ny utvärderingsmetod, Visual Grading Regression (VGR), som inte tidigare har använts vid optimeringsstudier inom nuklearmedicin. Syftet med arbetet är att optimera aktivitetsnivån för regionala blodfödesundersökningar med gammakamera med avseende på bildkvalitet och stråldos till patient. I studien ingick 21 konsekutivt utvalda patienter med demensfrågeställning som alla genomgått en blodflödesundersökning av hjärnan med gammakameratomografi. En aktivitetsmängd på 1000 MBq injicerades till samtliga patienter. Genom att dela upp insamlingstiden i delmängder är det möjligt att generera flera bilder, vilka motsvarar olika mängder administrerad aktivitet, från en och samma undersökning. Från en studie genererades fem bilder, vilka motsvarade aktivitetsnivåer av 500, 625, 750, 875 och 1000 MBq. Kliniskt relevanta bildkriterier definierades i samarbete med en erfaren radiolog. Bilderna, motsvarande de olika aktivitetsnivåerna, bedömdes med en fyrgradig skala utifrån uppfyllandet av de definierade kriterierna. Tre erfarna radiologer med specialistkompetens inom nuklearmedicin deltog som observatörer i studien och granskade bilderna en och en i en slumpmässigt vald ordning. Resultatet av bedömningen analyserades med hjälp av den valda utvärderingsmetoden, VGR, vilken är speciellt utformad för visuella granskningsstudier och har fördelen att kunna ta hänsyn till variationer mellan patienter och mellan observatörer. Resultatet visar att en skillnad i bildkvalitet kan ses mellan bilder som motsvarar en injicerad aktivitet på 500 MBq och 1000 MBq i fem av de sju kriterierna. Ingen skillnad kan ses mellan någon av de andra aktivitetsnivåerna och referensaktiviteten, en administrerad aktivitet på 1000 MBq. Studien visar inte att någon av de andra aktivitetsnivåerna ger samma bildkvalitet som 1000 MBq, endast på grund av att ingen skillnad sågs, men det ger en indikation på att aktivitetsnivån kan sänkas utan att förlora alltför mycket diagnostisk information

Optimization of iterative reconstruction parameters with attenuation correction, scatter correction and resolution recovery in myocardial perfusion SPECT/CT

Objective: The aim of this study was to characterize the optimal reconstruction parameters for ordered-subset expectation maximization (OSEM) with attenuation correction, scatter correction, and depth-dependent resolution recovery (OSEMACSCRR). We assessed the optimal parameters for OSEMACSCRR in an anthropomorphic torso phantom study, and evaluated the validity of the reconstruction parameters in the groups of normal volunteers and patients with abnormal perfusion. Methods: Images of the anthropomorphic torso phantom, 9 normal volunteers and 7 patients undergoing myocardial perfusion SPECT were acquired with a SPECT/CT scanner. SPECT data comprised a 64 × 64 matrix with an acquisition pixel size of 6.6 mm. A normalized mean square error (NMSE) of the phantom image was calculated to determine both optimal OSEM update and a full width at half maximum (FWHM) of Gaussian filter. We validated the myocardial count, contrast and noise characteristic for clinical subjects derived from OSEMACSCRR processing. OSEM with depth-dependent resolution recovery (OSEMRR) and filtered back projection (FBP) were simultaneously performed to compare OSEMACSCRR. Results: The combination of OSEMACSCRR with 90-120 OSEM updates and Gaussian filter with 13.2-14.85 mm FWHM yielded low NMSE value in the phantom study. When we used OSEMACSCRR with 120 updates and Gaussian filter with 13.2 mm FWHM in the normal volunteers, myocardial contrast showed significantly higher value than that derived from 120 updates and 14.85 mm FWHM. OSEMACSCRR with the combination of 90-120 OSEM updates and 14.85 mm FWHM produced lowest % root mean square (RMS) noise. Regarding the defect contrast of patients with abnormal perfusion, OSEMACSCRR with the combination of 90-120 OSEM updates and 13.2 mm FWHM produced significantly higher value than that derived from 90-120 OSEM updates and 14.85 mm FWHM. OSEMACSCRR was superior to FBP for the % RMS noise (8.52 ± 1.08 vs. 9.55 ± 1.71, p = 0.02) and defect contrast (0.368 ± 0.061 vs. 0.327 ± 0.052, p = 0.01), respectively. Conclusions: Clinically optimized the number of OSEM updates and FWHM of Gaussian filter were (1) 120 updates and 13.2 mm, and (2) 90-120 updates and 14.85 mm on the OSEMACSCRR processing, respectively. Further assessment may be required to determine the optimal iterative reconstruction parameters in a larger patient population. © 2013 The Japanese Society of Nuclear Medicine